Efficacy and Safety of Pegzilarginase in Patients With Arginase 1 Deficiency

Completed · Phase 3 · Has a placebo group

Conditions studied: Arginase I Deficiency, Hyperargininemia

In brief

CAEB1102-300A is a multi-center randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of pegzilarginase in patients with ARG1-D. This study will consist of a screening period; a randomized, double-blind treatment period; a long-term extension; and a follow up visit for final safety assessments.

Key facts

Study ID

NCT03921541

Run by

Aeglea Biotherapeutics

People needed

32

Starts

2019-04-10

Expected to finish

2023-01-27

Last updated by the study team

2024-11-19

Who can join

Age: 2 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects are eligible to be included in the study only if all the following criteria apply:
• The subject and/or parent/guardian provides written informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• A current diagnosis of ARG1 D as documented in medical records, which must include 1 of the following: elevated plasma arginine levels, a mutation analysis that results in a pathogenic variant, or reduced RBC arginase activity. For entry into this study, subjects must also fulfill the following plasma arginine criteria:
• The average of all measured values of plasma arginine during the screening period prior to the randomization visit (Visit 1, Study Day 1) is ≥ 250 µmol/L
• If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period
• Subjects must be ≥ 2 years of age on the date of informed consent/assent
• The subject must be assessable for clinically meaningful within-subject change (clinical response) on at least one component of one assessment included in the key secondary/other secondary endpoints. To be considered assessable, the subject must be able to complete the assessment, and must have a baseline deficit in at least one component as defined in the protocol
• Have received documented confirmation from the investigator and/or dietician that the subject can maintain their diet in accordance with dietary information presented in the protocol, ie, can maintain the current level of protein consumption, including natural protein and EAA supplementation
• Subjects receiving ammonia scavenger therapy, anti-epileptic drugs, and/or medications for spasticity (eg, baclofen) must be on a stable dose of the medication for at least 4 weeks prior to randomization and be willing to remain on a stable dose during the double-blind portion and blinded follow-up portions of the study
• Female and male subjects may participate. Female subjects of childbearing potential must have a negative serum pregnancy test during the screening period before receiving the first dose of study treatment, and a negative urine pregnancy test on the day of the first dose, prior to the first dose. If the subject (male or female) is engaging in sexual activity that could lead to pregnancy, must be surgically sterile, postmenopausal (no menses for 12 months without an alternative medical cause or a high FSH level in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy), or must agree to use a highly effective method of birth control during the study and for a minimum of 30 days after the last study drug administration. Highly effective methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progesterone-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); or abstinence (refraining from heterosexual intercourse during the entire period of risk associated with study treatment).

You may not qualify if…

• Hyperammonemic episode (defined as an event in which a subject has an ammonia level ≥100 µM with one or more symptoms related to hyperammonemia requiring hospitalization or emergency room management) within the 6 weeks before the first dose of study drug is administered
• Active infection requiring anti-infective therapy within 3 weeks prior to first dose
• Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Extreme mobility deficit, defined as either the inability to be assessed on the GFAQ or a score of 1 on the GFAQ
• Other medical conditions or comorbidities that, in the opinion of the investigator would interfere with study compliance or data interpretation (eg, severe intellectual disability precluding required study assessments)
• Has participated in a previous interventional study with pegzilarginase
• Has a history of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events
• Subject is being treated with botulinum toxin-containing regimens or plans to initiate such regimens during the double-blind or blinded follow-up portions of the study or received surgical or botulinum-toxin treatment for spasticity-related complications within the 16 weeks prior to the first dose of study treatment in this study
• Is currently participating in another therapeutic clinical trial or has received any investigational agent within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study treatment in this study
• Previous liver or hematopoietic transplant procedure.

Where it is running

• Harvey Pediatrics — Rogers, Arkansas, United States
• Children's Hospital of Orange County — Orange, California, United States
• Stanford University School of Medicine — Stanford, California, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• University of Florida College of Medicine — Gainesville, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States
• Icahn School of Medicine at Mount Sinai — New York, New York, United States
• Cohen Children's Medical Center (Northwell Health) — Queens, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• UT Southwestern Medical Center — Dallas, Texas, United States
• University of Texas Health Science Center Medical School at Houston — Houston, Texas, United States
• University of Utah Hospitals & Clinics — Salt Lake City, Utah, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• LKH Bregenz — Bregenz, Austria
• Medizinische Universität Innsbruck — Innsbruck, Austria
• McGill University Health Center — Montreal, Quebec, Canada
• Hôpital Necker - Enfants Malades — Paris, France
• Hopital des Enfants — Talence, France
• Universitaetsklinikum Muenster — Münster, North Rhine-Westphalia, Germany
• Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz — Mainz, Rhineland-Palatinate, Germany
• Fondazione MBBM — Monza, Italy

Full record on ClinicalTrials.gov

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